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Open-Label Extension Study of Trofinetide for the Treatment of Girls and Women With Rett Syndrome (LILAC™)

Primary Purpose

Rett Syndrome

Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Trofinetide
Sponsored by
ACADIA Pharmaceuticals Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Rett Syndrome

Eligibility Criteria

5 Years - 21 Years (Child, Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

  1. Has completed the Week 12/End-of-treatment visit of the antecedent study, Study ACP-2566-003
  2. Met all entry criteria for the antecedent study
  3. May benefit from long-term treatment with open-label trofinetide in the judgment of the Investigator
  4. Can still swallow the study medication provided as a liquid solution or can take it by gastrostomy tube
  5. The subject's caregiver is English-speaking and has sufficient language skills to complete the caregiver assessments
  6. Subject and caregiver(s) must reside at a location to which study drug can be delivered and have been at their present residence for at least 3 months prior to Baseline

Exclusion Criteria:

  1. Began treatment with growth hormone during the antecedent study
  2. Began treatment with IGF-1 during the antecedent study
  3. Began treatment with insulin during the antecedent study
  4. Has developed a clinically significant cardiovascular, endocrine (such as hypo- or hyperthyroidism, Type 1 diabetes mellitus, or uncontrolled Type 2 diabetes mellitus), renal, hepatic, respiratory, or gastrointestinal disease (such as celiac disease or inflammatory bowel disease) or has major surgery planned during the study
  5. Subject is judged by the Investigator or the Medical Monitor to be inappropriate for the study due to AEs, medical condition, or noncompliance with investigational product or study procedures in the antecedent study
  6. Has a clinically significant abnormality in vital signs at Baseline
  7. Has a QTcF interval of >450 ms on the Baseline ECG performed before the first dose of trofinetide is given in the present study
  8. Has developed a clinically significant ECG finding during the antecedent study

Additional inclusion/exclusion criteria apply. Patients will be evaluated at baseline to ensure that all criteria for study participation are met. Patients may be excluded from the study based on these assessments (and specifically, if it is determined that their baseline health and condition do not meet all prespecified entry criteria).

Sites / Locations

  • University of Alabama at Birmingham
  • Translational Genomics Research Institute (TGen)
  • University of California, San Diego
  • UC Davis MIND Institute
  • Children's Hospital Colorado
  • Children Medical Services
  • Emory Genetics Clinical Trial Center
  • Rush University Medical Center
  • Kennedy Krieger Institute - Clinical Trials Unit
  • Boston Children's Hospital
  • Gillette Children's Specialty Healthcare
  • Washington University School of Medicine, St. Louis Children's Hospital
  • Montefiore Medical Center, Children's Hospital at Montefiore
  • The University of North Carolina at Chapel Hill
  • Cincinnati Children's Hospital Medical Center
  • Cleveland Clinic
  • Children's Hospital of Philadelphia
  • Greenwood Genetic Center
  • Vanderbilt University Medical Center
  • Texas Children's Hospital
  • Seattle Children's

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Trofinetide

Arm Description

Outcomes

Primary Outcome Measures

Percentage of subjects with treatment-emergent adverse events (TAEs), percentage of subjects with serious adverse events (SAEs), and percentage of subjects withdrawals due to adverse events (AEs)
Number of subjects with post-Baseline potentially clinically important changes in ECG
Percentage of subjects with post-Baseline potentially clinically important changes in ECG
Number of subjects with post-Baseline potentially clinically important changes in vital signs
Percentage of subjects with post-Baseline potentially clinically important changes in vital signs
Number of subjects with post-Baseline potentially clinically important changes in body weight
Percentage of subjects with post-Baseline potentially clinically important changes in body weight
Number of subjects with post-Baseline potentially clinically important changes in laboratory parameters
Percentage of subjects with post-Baseline potentially clinically important changes in laboratory parameters

Secondary Outcome Measures

Rett Syndrome Behaviour Questionnaire (RSBQ) total score - change from Baseline to Week 40
The scale includes 45 items, 39 of them grouped into 8 subscales, whose ratings reflect the severity and frequency of symptoms. Items are rated as "0" (not true), "1" (somewhat or sometimes true), or "2" (very true). The 8 subscales include general mood, breathing problems, hand behavior, face movements, body rocking/expressionless face, night-time behaviors, fear/anxiety, and walking/standing.
Clinical Global Impression-Improvement (CGI-I) score at Week 40
To rate how much the subject's illness has improved or worsened relative to a baseline state, a 7-point scale is used from 1=very much improved, 2=much improved, 3=minimally improved, 4=no change, 5=minimally worse, 6=much worse, 7=very much worse.
Change from Baseline to Week 40 in Communication and Symbolic Behavior Scales Developmental Profile™ Infant-Toddler Checklist - Social Composite Score (CSBS-DP-IT Social)
Standardized screening scale for assessing communication and pre-linguistic skills in young children 12-24 months and can be used with older children with developmental delay. The CSBS-DP includes a suite of three separate measures: The Infant-Toddler Checklist, a follow-up Caregiver Questionnaire and a Behavior Sample. In this study only the Infant-Toddler (CSBS-DP-IT) Checklist will be used. The CSBS-DP-IT Checklist is a 24-item rating scale and each item is scored using a three-level rating of frequency: "not yet", "sometimes" and "often". Three composite scores assessing 7 skill areas can be calculated: 1) Social Composite (including Emotion and Eye Gaze, Communication Rate and Function, and Gestures); 2) Speech Composite (including Sounds and Words); 3) Symbolic Composite (including Understanding and Object Use).
Change from Baseline to Week 40 in Overall Quality of Life Rating of the Impact of Childhood Neurologic Disability Scale (ICND)
The scale evaluates the effect of four conditions or health problems on 11 aspects of a child's or family's life as "A lot", "Some", "A little", "Not at all", or "Does not apply". The four conditions or health problems are 1) inattentiveness, impulsivity, or mood, 2) ability to think and remember, 3) neurologic or physical limitations, and 4) epilepsy. The overall quality of life of the subject is also rated by responding to the following: "Please rate your child's overall 'Quality of Life' on the scale below. Choose the number which you feel is best and circle it." The choices range from 1 ("Poor") to 6 ("Excellent").
Change from Baseline to Week 40 in Rett Syndrome Clinician Rating of Hand Function (RTT-HF)
Clinical assessment of the subject's ability to use their hands for functional purposes (such as reaching for and grasping objects, self-feeding, or drawing). The assessment is made on an 8-point Likert scale (0-7) with 0 denoting normal functioning and 7 the most severe impairment.
Change from Baseline to Week 40 in Rett Syndrome Clinician Rating of Ambulation and Gross Motor Skills (RTT-AMB)
Clinical assessment of the subject's ability to sit, stand, and ambulate (e.g., walking, running, climbing stairs). The assessment is made on an 8-point Likert scale (0-7) with 0 denoting normal functioning and 7 the most severe impairment.
Change from Baseline to Week 40 in Rett Syndrome Clinician Rating of Ability to Communicate Choices (RTT-COMC)
Clinical assessment of the subject's ability to communicate their choices or preferences, which can include the use of nonverbal means such as eye contact or gestures. The assessment is made on an 8-point Likert scale (0-7) with 0 denoting normal functioning and 7 the most severe impairment.
Change from Baseline to Week 40 in Rett Syndrome Clinician Rating of Verbal Communication (RTT-VCOM)
Clinical assessment of the subject's ability to communicate verbally (e.g., words and phrases). The assessment is made on an 8-point Likert scale (0-7) with 0 denoting normal functioning and 7 the most severe impairment.
Change from Baseline to Week 40 in Clinical Global Impression-Severity (CGI-S)
A 7 point scale that rates the severity of the subject's illness at the time of assessment, relative to the clinician's experience with subjects who have the same diagnosis. A subject is assessed on severity of illness at the time of rating: 1=normal, not at all ill; 2=borderline ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; or 7= extremely ill.
Change from Baseline to Week 40 in Rett Syndrome Caregiver Burden Inventory (RTT-CBI) Total Score (items 1-24)
The scale is intended to directly address caregiver burden and indirectly assess the significance of treatment effects on function in the context of activities of daily living. Ratings are on a 5-point Likert scale including: 0-never; 1-rarely; 2-sometimes; 3-frequently and 4-nearly always. As in the original Caregiver Burden Inventory, the RTT-CBI has 24 negatively worded items (items 1 through 24) yielding a total score up to 96.
Change from Baseline to Week 40 in Impact of Childhood Neurologic Disability Scale (ICND) Total Score
The scale evaluates the effect of four conditions or health problems on 11 aspects of a child's or family's life as "A lot", "Some", "A little", "Not at all", or "Does not apply". The four conditions or health problems are 1) inattentiveness, impulsivity, or mood, 2) ability to think and remember, 3) neurologic or physical limitations, and 4) epilepsy. The overall quality of life of the subject is also rated by responding to the following: "Please rate your child's overall 'Quality of Life' on the scale below. Choose the number which you feel is best and circle it." The choices range from 1 ("Poor") to 6 ("Excellent").

Full Information

First Posted
February 19, 2020
Last Updated
September 21, 2022
Sponsor
ACADIA Pharmaceuticals Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT04279314
Brief Title
Open-Label Extension Study of Trofinetide for the Treatment of Girls and Women With Rett Syndrome
Acronym
LILAC™
Official Title
A 40-Week, Open-label Extension Study of Trofinetide for the Treatment of Girls and Women With Rett Syndrome
Study Type
Interventional

2. Study Status

Record Verification Date
September 2022
Overall Recruitment Status
Completed
Study Start Date
January 29, 2020 (Actual)
Primary Completion Date
August 19, 2022 (Actual)
Study Completion Date
August 19, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
ACADIA Pharmaceuticals Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
To investigate the safety and tolerability of long-term treatment with oral trofinetide in girls and women with Rett syndrome

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rett Syndrome

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
154 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Trofinetide
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Trofinetide
Intervention Description
Trofinetide solution of 30-60 mL based on subject's weight at Baseline, administered twice daily by mouth or gastrostomy tube (G-tube)
Primary Outcome Measure Information:
Title
Percentage of subjects with treatment-emergent adverse events (TAEs), percentage of subjects with serious adverse events (SAEs), and percentage of subjects withdrawals due to adverse events (AEs)
Time Frame
40 Weeks Treatment Duration
Title
Number of subjects with post-Baseline potentially clinically important changes in ECG
Time Frame
40 Weeks Treatment Duration
Title
Percentage of subjects with post-Baseline potentially clinically important changes in ECG
Time Frame
40 Weeks Treatment Duration
Title
Number of subjects with post-Baseline potentially clinically important changes in vital signs
Time Frame
40 Weeks Treatment Duration
Title
Percentage of subjects with post-Baseline potentially clinically important changes in vital signs
Time Frame
40 Weeks Treatment Duration
Title
Number of subjects with post-Baseline potentially clinically important changes in body weight
Time Frame
40 Weeks Treatment Duration
Title
Percentage of subjects with post-Baseline potentially clinically important changes in body weight
Time Frame
40 Weeks Treatment Duration
Title
Number of subjects with post-Baseline potentially clinically important changes in laboratory parameters
Time Frame
40 Weeks Treatment Duration
Title
Percentage of subjects with post-Baseline potentially clinically important changes in laboratory parameters
Time Frame
40 Weeks Treatment Duration
Secondary Outcome Measure Information:
Title
Rett Syndrome Behaviour Questionnaire (RSBQ) total score - change from Baseline to Week 40
Description
The scale includes 45 items, 39 of them grouped into 8 subscales, whose ratings reflect the severity and frequency of symptoms. Items are rated as "0" (not true), "1" (somewhat or sometimes true), or "2" (very true). The 8 subscales include general mood, breathing problems, hand behavior, face movements, body rocking/expressionless face, night-time behaviors, fear/anxiety, and walking/standing.
Time Frame
40 Weeks Treatment Duration
Title
Clinical Global Impression-Improvement (CGI-I) score at Week 40
Description
To rate how much the subject's illness has improved or worsened relative to a baseline state, a 7-point scale is used from 1=very much improved, 2=much improved, 3=minimally improved, 4=no change, 5=minimally worse, 6=much worse, 7=very much worse.
Time Frame
40 Weeks Treatment Duration
Title
Change from Baseline to Week 40 in Communication and Symbolic Behavior Scales Developmental Profile™ Infant-Toddler Checklist - Social Composite Score (CSBS-DP-IT Social)
Description
Standardized screening scale for assessing communication and pre-linguistic skills in young children 12-24 months and can be used with older children with developmental delay. The CSBS-DP includes a suite of three separate measures: The Infant-Toddler Checklist, a follow-up Caregiver Questionnaire and a Behavior Sample. In this study only the Infant-Toddler (CSBS-DP-IT) Checklist will be used. The CSBS-DP-IT Checklist is a 24-item rating scale and each item is scored using a three-level rating of frequency: "not yet", "sometimes" and "often". Three composite scores assessing 7 skill areas can be calculated: 1) Social Composite (including Emotion and Eye Gaze, Communication Rate and Function, and Gestures); 2) Speech Composite (including Sounds and Words); 3) Symbolic Composite (including Understanding and Object Use).
Time Frame
40 Weeks Treatment Duration
Title
Change from Baseline to Week 40 in Overall Quality of Life Rating of the Impact of Childhood Neurologic Disability Scale (ICND)
Description
The scale evaluates the effect of four conditions or health problems on 11 aspects of a child's or family's life as "A lot", "Some", "A little", "Not at all", or "Does not apply". The four conditions or health problems are 1) inattentiveness, impulsivity, or mood, 2) ability to think and remember, 3) neurologic or physical limitations, and 4) epilepsy. The overall quality of life of the subject is also rated by responding to the following: "Please rate your child's overall 'Quality of Life' on the scale below. Choose the number which you feel is best and circle it." The choices range from 1 ("Poor") to 6 ("Excellent").
Time Frame
40 Weeks Treatment Duration
Title
Change from Baseline to Week 40 in Rett Syndrome Clinician Rating of Hand Function (RTT-HF)
Description
Clinical assessment of the subject's ability to use their hands for functional purposes (such as reaching for and grasping objects, self-feeding, or drawing). The assessment is made on an 8-point Likert scale (0-7) with 0 denoting normal functioning and 7 the most severe impairment.
Time Frame
40 Weeks Treatment Duration
Title
Change from Baseline to Week 40 in Rett Syndrome Clinician Rating of Ambulation and Gross Motor Skills (RTT-AMB)
Description
Clinical assessment of the subject's ability to sit, stand, and ambulate (e.g., walking, running, climbing stairs). The assessment is made on an 8-point Likert scale (0-7) with 0 denoting normal functioning and 7 the most severe impairment.
Time Frame
40 Weeks Treatment Duration
Title
Change from Baseline to Week 40 in Rett Syndrome Clinician Rating of Ability to Communicate Choices (RTT-COMC)
Description
Clinical assessment of the subject's ability to communicate their choices or preferences, which can include the use of nonverbal means such as eye contact or gestures. The assessment is made on an 8-point Likert scale (0-7) with 0 denoting normal functioning and 7 the most severe impairment.
Time Frame
40 Weeks Treatment Duration
Title
Change from Baseline to Week 40 in Rett Syndrome Clinician Rating of Verbal Communication (RTT-VCOM)
Description
Clinical assessment of the subject's ability to communicate verbally (e.g., words and phrases). The assessment is made on an 8-point Likert scale (0-7) with 0 denoting normal functioning and 7 the most severe impairment.
Time Frame
40 Weeks Treatment Duration
Title
Change from Baseline to Week 40 in Clinical Global Impression-Severity (CGI-S)
Description
A 7 point scale that rates the severity of the subject's illness at the time of assessment, relative to the clinician's experience with subjects who have the same diagnosis. A subject is assessed on severity of illness at the time of rating: 1=normal, not at all ill; 2=borderline ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; or 7= extremely ill.
Time Frame
40 Weeks Treatment Duration
Title
Change from Baseline to Week 40 in Rett Syndrome Caregiver Burden Inventory (RTT-CBI) Total Score (items 1-24)
Description
The scale is intended to directly address caregiver burden and indirectly assess the significance of treatment effects on function in the context of activities of daily living. Ratings are on a 5-point Likert scale including: 0-never; 1-rarely; 2-sometimes; 3-frequently and 4-nearly always. As in the original Caregiver Burden Inventory, the RTT-CBI has 24 negatively worded items (items 1 through 24) yielding a total score up to 96.
Time Frame
40 Weeks Treatment Duration
Title
Change from Baseline to Week 40 in Impact of Childhood Neurologic Disability Scale (ICND) Total Score
Description
The scale evaluates the effect of four conditions or health problems on 11 aspects of a child's or family's life as "A lot", "Some", "A little", "Not at all", or "Does not apply". The four conditions or health problems are 1) inattentiveness, impulsivity, or mood, 2) ability to think and remember, 3) neurologic or physical limitations, and 4) epilepsy. The overall quality of life of the subject is also rated by responding to the following: "Please rate your child's overall 'Quality of Life' on the scale below. Choose the number which you feel is best and circle it." The choices range from 1 ("Poor") to 6 ("Excellent").
Time Frame
40 Weeks Treatment Duration

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
5 Years
Maximum Age & Unit of Time
21 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Has completed the Week 12/End-of-treatment visit of the antecedent study, Study ACP-2566-003 Met all entry criteria for the antecedent study May benefit from long-term treatment with open-label trofinetide in the judgment of the Investigator Can still swallow the study medication provided as a liquid solution or can take it by gastrostomy tube The subject's caregiver is English-speaking and has sufficient language skills to complete the caregiver assessments Subject and caregiver(s) must reside at a location to which study drug can be delivered and have been at their present residence for at least 3 months prior to Baseline Exclusion Criteria: Began treatment with growth hormone during the antecedent study Began treatment with IGF-1 during the antecedent study Began treatment with insulin during the antecedent study Has developed a clinically significant cardiovascular, endocrine (such as hypo- or hyperthyroidism, Type 1 diabetes mellitus, or uncontrolled Type 2 diabetes mellitus), renal, hepatic, respiratory, or gastrointestinal disease (such as celiac disease or inflammatory bowel disease) or has major surgery planned during the study Subject is judged by the Investigator or the Medical Monitor to be inappropriate for the study due to AEs, medical condition, or noncompliance with investigational product or study procedures in the antecedent study Has a clinically significant abnormality in vital signs at Baseline Has a QTcF interval of >450 ms on the Baseline ECG performed before the first dose of trofinetide is given in the present study Has developed a clinically significant ECG finding during the antecedent study Additional inclusion/exclusion criteria apply. Patients will be evaluated at baseline to ensure that all criteria for study participation are met. Patients may be excluded from the study based on these assessments (and specifically, if it is determined that their baseline health and condition do not meet all prespecified entry criteria).
Facility Information:
Facility Name
University of Alabama at Birmingham
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35223
Country
United States
Facility Name
Translational Genomics Research Institute (TGen)
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85012
Country
United States
Facility Name
University of California, San Diego
City
La Jolla
State/Province
California
ZIP/Postal Code
92093
Country
United States
Facility Name
UC Davis MIND Institute
City
Sacramento
State/Province
California
ZIP/Postal Code
95817
Country
United States
Facility Name
Children's Hospital Colorado
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Children Medical Services
City
Tampa
State/Province
Florida
ZIP/Postal Code
33606
Country
United States
Facility Name
Emory Genetics Clinical Trial Center
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
Rush University Medical Center
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Facility Name
Kennedy Krieger Institute - Clinical Trials Unit
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21205
Country
United States
Facility Name
Boston Children's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Gillette Children's Specialty Healthcare
City
Saint Paul
State/Province
Minnesota
ZIP/Postal Code
55101
Country
United States
Facility Name
Washington University School of Medicine, St. Louis Children's Hospital
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Montefiore Medical Center, Children's Hospital at Montefiore
City
Bronx
State/Province
New York
ZIP/Postal Code
10467
Country
United States
Facility Name
The University of North Carolina at Chapel Hill
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599
Country
United States
Facility Name
Cincinnati Children's Hospital Medical Center
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45229
Country
United States
Facility Name
Cleveland Clinic
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
Children's Hospital of Philadelphia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Greenwood Genetic Center
City
Greenwood
State/Province
South Carolina
ZIP/Postal Code
29626
Country
United States
Facility Name
Vanderbilt University Medical Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
Facility Name
Texas Children's Hospital
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Seattle Children's
City
Seattle
State/Province
Washington
ZIP/Postal Code
98105
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Open-Label Extension Study of Trofinetide for the Treatment of Girls and Women With Rett Syndrome

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